Based on prior studies that have shown that physical activity is beneficial to cognitive health, we plan to examine the effects of daily non-exercise physical activity on cognitive function in the elderly. Specifically, we propose to: 1) more accurately identify daily levels of physical activity using ambient in-home monitoring;2) establish non- exercise physical activity as a protective factor against cognitive decline;and 3) identify activity related biomarkers that will assist in the detection of cognitive impairment and provide potential targets for intervention. Plan: This proposed study will use previously collected data from the Intelligent Systems for Assessing Aging Change (ISAAC) study, a longitudinal cohort that uses new technologies to assess the changes in behavior, health and cognition that occur with aging. There are currently over 230 subjects enrolled who undergo standardized yearly clinical and neuropsychological evaluations. Physical activity is measured by motion sensors that are strategically installed throughout subjects'homes and allow unobtrusive measurement of physical activity and walking. Biomarkers of interest that will be analyzed in this proposal include leptin, orexin, brain-derived neurotrophic factor, insulin- like growth factor 1, and highly sensitive CRP. Methods: Physical activity measures (e.g., gait speed, walks per day, total activity, and others) will be compared between cognitively intact subjects and those with mild cognitive impairment (MCI) using univariate analysis and multivariate linear regression controlling for confounders, such as age, gender, education, BMI and health conditions that affect mobility. Next, we will assess the association between baseline physical activity levels and changes in domain-specific and global cognitive function at 12, 24 and 36 month follow-up time points from baseline using multivariate linear regression, mixed models and Cox proportional hazards. Finally, the associations between biomarker levels, physical activity and cognitive status will be examined with using multivariate linear regression, mixed models and Cox proportional hazards. Findings to Date: Physical activity, including aerobic exercise and low-level activity such as walking, has been shown to improve cognitive function and lower the risk of incident dementia. The level of physical activity that is required to see benefits remains unclear. Relevance to VA's Mission: As the aging veteran population increases, the prevalence of dementia in the veteran population can also be expected to greatly increase over the coming decade and this will have an enormous impact on the VA Health System. The cost of care for cognitively impaired veterans is estimated to be three times greater than for veterans who are not cognitively impaired. Veterans with dementia make greater use of inpatient services, VA-operated nursing homes, and VA sponsored home care services. Early interventions to delay or treat cognitive impairment will reduce costs and improve the quality of care for aging veterans. PUBLIC HEALTH RELEVANCE: The prevalence of dementia in the VA health system is estimated to be 7.3% (53) and this number is expected to greatly increase over the next decade as the number of veterans over age 65 grows. Cognitive impairment places significant financial and social burden on both caregivers and the VA health system. The research proposed is, at its core, critical to ultimately designing optimal activity-based interventions for maintaining cognitive health. It has the potential to benefit veterans, their caregivers and the VA by delaying or preventing the onset of cognitive impairment, allowing individuals to live independently longer, delaying long-term care placement and reducing dementia-related healthcare costs. This will reduce the burden on the VA healthcare system and caregivers as well improve quality of life for both patients and their caregivers. )